Clinical Stage Lead Candidate ‘Naked’ EVade™ RNases (QBI-139) — QBI-139, a variant of human RNase I, has demonstrated significant efficacy in a variety of in vivo models of human cancer, including breast, colon, non-small cell lung, ovarian, pancreatic and prostate. A Phase I trial of QBI-139 in refractory patients with solid tumors is ongoing at University of Texas M. D. Anderson Cancer Center and University of Wisconsin Carbone Cancer Center. The Phase I trial of QBI-139 is a standard 3+3 dose escalation trial with a starting dose of 3 mg/m2. The drug was well tolerated in the most recent closed cohort (158 mg/m2), with promising clinical benefits.
Phase 1 Trial Expansion – The next planned cohort is intended to confirm Maximum Tolerated Dose in solid tumors and will be followed by determination of the safety of QBI-139 in combination with a standard of care (SOC) regimen in a defined patient population. The majority of patients (~20) will be enrolled in the final expansion cohort to determine the efficacy of QBI-139 in combination with SOC. The target patient population will be selected based on preclinical and clinical results as well as analysis of markets and regulatory issues. The dose expansion cohort will be targeted at one of the following indications: second or third line non-small cell lung cancer regardless of mutation status in combination with a platinum doublet, second line platinum refractory/resistant ovarian cancer in combination with a platinum doublet or post-androgen receptor antagonist in hormone resistant prostate cancer (HRPC) in combination with a (SOC) agent. Final indication selection will depend on the focus and experience of the partner organization. As an example, HRPC has an evolving treatment paradigm with a unique system for treatment delivery and navigating this approach would benefit from significant domain experience. Each indication is anticipated to have similar enrolment (~40 patients), costs (approximately $7M) and timelines (30 months).
Data from First-in-Human Phase 1 Trial
While the MTD has not been conclusively established to date, the first-in-human portion of the solid tumors Phase I trial of QBI-139 achieved significant milestones, including:
- Manageable dose-dependent adverse events (notably no myelosuppression nor kidney toxicity),
- Dose and exposure levels similar to levels efficacious in animal models and
- Suggestions of efficacy in recent cohorts.
Competitive Advantages — To date, the data support the use of QBI-139 as a broadly effective anti-cancer agent with a good therapeutic window. While tumor growth inhibition of greater than fifty percent was seen in a variety of xenograft models, toxicities commonly associated with chemotherapy (e.g. myelosuppression, mucositis, alopecia) have not been seen in non-clinical studies. After multiple dose levels of escalation, these events have also not been identified in the Phase I human clinical trial of QBI-139. These features position the drug well relative to traditional chemotherapy and targeted therapies. Some key highlights are:
- QBI-139 kills cancer cells by a novel mechanism – destruction of RNA
- QBI-139 works in combination with small molecule chemotherapeutics, such as vincristine and cisplatin
- The therapeutic index of QBI-139 is unlikely to be curtailed by efflux pumps
- QBI-139 is a broadly active drug with strong therapeutic index
Quintessence Biosciences, Inc. 